Glucose restriction induced by intermittent fasting promotes alternative metabolic fluxes leading to memory CD8+ T cell development
7 affiliations
- 1Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
- 2The Gene Lay Institute of Immunology and Inflammation, Harvard Medical School and Brigham and Women’s Hospital, Boston, USA.
- 3Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
- 4Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Density, Seoul National University, Seoul 08826, Republic of Korea.
- 5Department of Microbiology and Immunology and Medical Research Center for Combinatorial Tumor Immunotherapy, Chonnam National University Medical School, Hwasun 58128, Republic of Korea.
- 6Institutes of Green Bio Science & Technology, Seoul National University, Pyeongchang 25354, Republic of Korea.
- 7Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea.
Abstract
Dietary restrictions are increasingly recognized as modulators of immune cell function. However, how they shape CD8⁺ T cell fate decisions remains incompletely understood. Here, we investigated the impact of intermittent fasting (IF) on differentiation of heterogeneous effector T cell subsets and the formation of a long-lived homeostatic memory pool. We found that IF skewed CD8⁺ T cell differentiation toward memory precursor effector cells (MPECs) and enhanced the central memory CD8⁺ T cell development and functions. Mechanistically, glucose restriction induced by IF promotes alternative metabolic fluxes leading to fatty acid oxidation. This metabolic shift enhanced mitochondrial fitness and supported MPEC differentiation via metabolic-epigenetic cross-talk, culminating in durable and functionally robust memory CD8⁺ T cell responses. Applying this strategy in adoptive transfer therapy, intratumoral defects could be circumvented by imprinting a memory phenotype under IF-mimicking conditions, resulting in improved and long-lasting antitumor activity. Collectively, these findings underscore the importance of IF in orchestrating metabolic-epigenetic cross-talk to enhance memory formation and antitumor immunity.
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BibTeX
@article{park2026glucose,
title = {{Glucose restriction induced by intermittent fasting promotes alternative metabolic fluxes leading to memory CD8+ T cell development}},
author = {Da-Jeong Park and Young-Jun Ju and Young Jin Pyung and Cheol Gyun Kim and Narae Kim and MinJi Lim and Hyungseok Seo and Seung Hyun Han and Jae-Ho Cho and Cheol-Heui Yun},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aeg0361},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aeg0361},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Glucose restriction induced by intermittent fasting promotes alternative metabolic fluxes leading to memory CD8+ T cell development
AU - Da-Jeong Park
AU - Young-Jun Ju
AU - Young Jin Pyung
AU - Cheol Gyun Kim
AU - Narae Kim
AU - MinJi Lim
AU - Hyungseok Seo
AU - Seung Hyun Han
AU - Jae-Ho Cho
AU - Cheol-Heui Yun
PY - 2026
DA - 2026/10/28
JO - Science Advances
DO - 10.1126/sciadv.aeg0361
UR - https://www.science.org/doi/abs/10.1126/sciadv.aeg0361
AB - Dietary restrictions are increasingly recognized as modulators of immune cell function. However, how they shape CD8⁺ T cell fate decisions remains incompletely understood. Here, we investigated the impact of intermittent fasting (IF) on differentiation of heterogeneous effector T cell subsets and the formation of a long-lived homeostatic memory pool. We found that IF skewed CD8⁺ T cell differentiation toward memory precursor effector cells (MPECs) and enhanced the central memory CD8⁺ T cell development and functions. Mechanistically, glucose restriction induced by IF promotes alternative metabolic fluxes leading to fatty acid oxidation. This metabolic shift enhanced mitochondrial fitness and supported MPEC differentiation via metabolic-epigenetic cross-talk, culminating in durable and functionally robust memory CD8⁺ T cell responses. Applying this strategy in adoptive transfer therapy, intratumoral defects could be circumvented by imprinting a memory phenotype under IF-mimicking conditions, resulting in improved and long-lasting antitumor activity. Collectively, these findings underscore the importance of IF in orchestrating metabolic-epigenetic cross-talk to enhance memory formation and antitumor immunity.
SN - 2375-2548
ER -